The 395-residue proteolytic fragment E3, which comprises the two most C-terminal LG modules of the mouse laminin alpha1 chain, was previously shown to contain major binding sites for heparin, alpha-dystroglycan and sulfatides. The same fragment (alpha1LG4-5) and its individual alpha1LG4 and alpha1LG5 modules have now been obtained by recombinant production in mammalian cells.
These fragments were apparently folded into a native form, as shown by circular dichroism, electron microscopy and immunological assays. Fragment alpha1LG4-5 bound about five- to tenfold better to heparin, alpha-dystroglycan and sulfatides than E3. These binding activities could be exclusively localized to the alpha1LG4 module. Side-chain modifications and proteolysis demonstrated that Lys and Arg residues in the… C-terminal region of alpha1LG4 are essential for heparin binding. This was confirmed by 14 single to triple point mutations, which identified three non-contiguous basic regions (positions 2766-2770, 2791-2793, 2819-2820) as contributing to both heparin and sulfatide binding. Two of these regions were also recognized by monoclonal antibodies which have previously been shown to inhibit heparin binding.
The same three regions and a few additional basic residues also make major contributions to the binding of the cellular receptor alpha-dystroglycan, indicating a larger binding epitope. The data are also consistent with previous findings that heparin competes for alpha-dystroglycan binding.
Shared buffer switches consist of a memory pool completely shared among output ports of a switch. Shared buffer switches achieve low packet loss performance as buffer space is allocated in a flexible manner. However, this type of buffered switches suffers from high packet losses when the input traffic is imbalanced and bursty. Heavily loaded output ports dominate the usage of shared memory and lightly loaded ports cannot have access to these buffers.
To regulate the lengths of very active queues and avoid performance degradations, threshold‐based dynamic buffer management policy, decay function threshold, is proposed in this paper. Decay function threshold is a per‐queue threshold scheme that uses a tailored threshold for each output port queue. This scheme… suggests that buffer space occupied by an output port decays as the queue size of this port increases and/or empty buffer space decreases.
Results have shown that decay function threshold policy is as good as well‐known dynamic thresholds scheme, and more robust when multicast traffic is used. The main advantage of using this policy is that besides best‐effort traffic it provides support to quality of service (QoS) traffic by using an integrated buffer management and scheduling framework. Copyright © 2006 John Wiley & Sons, Ltd.
We consider the inverse problem in classification systems described as follows. Given a set of prototype cases representing a set of categories, a similarity function, and a new case classified in some category, we find the cost-minimizing changes to the attribute values such that the case is reclassified as a member of a (different) preferred category. The problem is “inverse” because the usual mapping is from a case to its unknown category.
The increased application of classification systems in business suggests that this inverse problem can be of significant benefit to decision makers as a form of sensitivity analysis. Analytic approaches to this inverse problem are difficult to formulate as the constraints are either not available or difficult to determine. To investigate this inverse… problem, we develop several genetic algorithms and study their performance as problem difficulty increases.
We develop a real genetic algorithm with feasibility control, a traditional binary genetic algorithm, and a steepest ascent hill climbing algorithm. In a series of simulation experiments, we compare the performance of these algorithms to the optimal solution as the problem difficulty increases (more attributes and classes). In addition, we analyze certain algorithm effects (level of feasibility control, operator design, and fitness function) to determine the best approach. Our results indicate the viability of the real genetic algorithm and the importance of feasibility control as the problem difficulty increases.
Previous attempts to use goal setting and feedback to improve safety behaviour on construction sites have focused on operatives, but recognized management commitment as essential for success. This research addressed two problems: validly and reliably measuring the safety performance of construction managers; and motivating managers to improve their safety performance.
A measure of management safety performance was developed, covering seven items: induction training; toolbox talk training; safety committees; subcontractor safety; maintenance of safety records; safety manager actions and safety consideration (interaction, communication and worker engagement). This was used on a case study site to improve motivation of the management team. During an intervention, using monthly feedback and… goal-setting techniques, their performance improved from 49% to 82% of maximum expected performance.
The results demonstrate that a valid and reliable measure of management safety performance is practicable and support the proposition that goal setting can improve management safety performance in the construction industry.
RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of these subsets casting doubt on their biological significance.;;In this study, we used a training-testing approach to test the reliability of cDNA microarray-based classifications of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA microarray.
Groups of genes were identified that were able to differentiate primary tumors from normal lung and lung metastases, as well as identify known histological subgroups of NSCLCs. Groups of genes were identified to discriminate sample clusters. A blinded confirmatory set of tumors was correctly classified by using these patterns. Some histologically… diagnosed large cell tumors were clearly classified by expression profile analysis as being either adenocarcinoma or squamous cell carcinoma, indicating that this group of tumors may not be genetically homogeneous.
High alpha-actinin-4 expression was identified as highly correlated with poor prognosis.;;These results demonstrate that gene expression profiling can identify molecular classes of resected NSCLCs that correctly classifies a blinded test cohort, and correlates with and supplements standard histological evaluation.